McGeer P L
Can J Physiol Pharmacol. 1984 Jul;62(7):741-54. doi: 10.1139/y84-123.
Aging does not affect tissues in a uniform fashion. Within the brain, substantial neuronal dropout occurs with age in the cholinergic medial basal forebrain complex, the noradrenergic locus coeruleus, and the dopaminergic substantia nigra pars compacta. These areas are also struck by diseases that are sharply age dependent. Alzheimer's disease causes neuronal destruction in the cholinergic cells of the medial basal forebrain and noradrenergic cells of the locus coeruleus. Parkinson's disease causes neuronal destruction mainly in the substantia nigra but with some destruction in the locus coeruleus. Parkinsonism-dementia affects all three areas. Alzheimer's disease is responsible for 50-60% of all cases of dementia. Severe dementia rises in frequency from less than 1% of the population at age 65-70 to over 15% by age 85. The cause of the disease is unknown. No method of prevention is known and present treatments are ineffective, although modest improvement has been reported for various therapeutic regimens designed to stimulate the cholinergic system. The neuronal systems identified as being affected in Alzheimer's disease and in the dementia of Parkinsonism correspond with those shown many years ago to be associated with the reticular activating system. This correspondence permits a new hypothesis of cognition and memory to be put forward, as well as a reinterpretation of data from animal research on the reticular activating system performed over a quarter of a century ago. The locus coeruleus is proposed as the noradrenergic element sensitizing the cortex to conscious recognition of real time events. The medial basal forebrain complex is proposed as the system registering the conscious event for storage and as the readout device when it is subsequently redisplayed in the cortex as memory. Storage could either be in the temporal lobe, in several areas of cortex with feedback to the medial basal forebrain, or in the cholinergic cells themselves.
衰老对组织的影响并不均匀。在大脑中，随着年龄增长，胆碱能内侧基底前脑复合体、去甲肾上腺素能蓝斑以及多巴胺能黑质致密部会出现大量神经元缺失。这些区域也易受与年龄密切相关的疾病侵袭。阿尔茨海默病会导致内侧基底前脑的胆碱能细胞以及蓝斑的去甲肾上腺素能细胞发生神经元破坏。帕金森病主要导致黑质的神经元破坏，但也会对蓝斑造成一些破坏。帕金森病痴呆会影响所有这三个区域。阿尔茨海默病占所有痴呆病例的50%至60%。重度痴呆的发病率从65至70岁人群中的不到1%上升至85岁时的超过15%。该病病因不明。目前尚无已知的预防方法，现有的治疗方法也无效，不过据报道，针对旨在刺激胆碱能系统的各种治疗方案有一定程度的改善。在阿尔茨海默病和帕金森病痴呆中被确定受影响的神经元系统，与多年前显示与网状激活系统相关的那些系统相对应。这种对应关系使得能够提出一种关于认知和记忆的新假说，以及对25年前进行的关于网状激活系统的动物研究数据进行重新解释。蓝斑被认为是使皮质对实时事件进行有意识识别敏感化的去甲肾上腺素能元素。内侧基底前脑复合体被认为是将有意识事件进行登记以便存储的系统，并且在该事件随后作为记忆在皮质中重新显示时作为读出装置。存储可能发生在颞叶、几个有反馈至内侧基底前脑的皮质区域，或者胆碱能细胞本身。
